PARABIOSIS IN THE CONTEXT OF DEGENERATIVE DISEASE AND AGING

 

 

By Krishna Patel

Texas A&M University


            Parabiosis is a 150-year-old surgical technique wherein two mice are anatomically joined and blood circulation is shared. In recent years, labs have revitalized this method, especially in the field of aging. Through numerous experiments, the circulation of young blood in an old mouse has shown to be beneficial in many aspects. Research in this field has brought hope to find cures for degenerative diseases in humans, like Alzheimer’s.

            Through parabiotic paring, scientists have found that young blood rejuvenates many tissues in the body. Specifically, growth and differentiation factor 11 (GDF11) affects the restorative process and has been recognized in young blood. With aging, there is a proportional decline in cognitive function and neurogenesis. It has been shown that young blood circulation leads to vascular remodeling, which slows age-related deterioration of the brain and increases neurogenesis.1

            Experiments have also shown a reversal of pre-existing neural conditions by increasing synaptic plasticity.2 Parabiosis can be used to examine aged progenitor cells, whose activity decreases with age. Satellite cells (precursors to skeletal muscle cells) can be regenerated and proliferated, allowing for better healing of muscles.3 Young hemocytoblasts (or blood stem cells) can heighten the rate and quality of fracture repair in the older population.4Moreover, restoring GDF11 in older mice can reverse cardiac hypertrophy, which is a common cause of heart failure in elderly people.5 Additionally, Type 2 diabetes becomes increasingly common with age because pancreatic β-cell proliferation decreases. Young blood circulation has also been shown to potentially increase the replication rate of old pancreatic β-cells,6 opening a new opportunity for treatment.

            In 2014, Tony Wyss-Coray resolved that young blood transfusions could be an alternative to parabiosis. He was inspired to do his study after seeing improved brain function and neurogenesis in old mice through parabiotic pairings. As the factor of youth appears to be in blood plasma, the method of young blood transfusion has the potential to work on people. Wyss-Coray started the company Alkahest in September 2014 in hopes to use young plasma to treat Alzheimer’s. Sakura Minami, a researcher at Alkahest, led a study to determine whether injecting young plasma from humans would have the same effect as parabiosis. In the experiment, blood samples from 18-year-old humans were injected twice a week into 12-month-old mice, which are equivalent to 50-year-old humans. After three weeks, the mice were submitted for testing. Minami found that the old mice ran around like young mice, had improved memory and cognition, and had increased neurogenesis in the hippocampus.7

            Ultimately, Alkahest hopes to pinpoint key proteins in plasma that aid in the revival of aged human tissues and manufacture a product that utilizes those proteins.8 There are currently trials taking place using young blood plasma in Alzheimer’s patients, expecting to reach the same favorable affects seen in the mice.

            As with most medical treatments, there are ethical issues to consider. Wyss-Coray himself has said that there is no clinical evidence that the treatment will necessarily be beneficial as it is still a new research method. Another issue that comes to mind is distributive justice. Currently, 21 million blood components are transfused every year in the U.S.9 Will using blood plasma for anti-aging purposes put a strain on supplies that could be used for patients who need them for other life threatening conditions? Consideration should also be placed on how compensations should change for those who donate in order to keep up with an increased demand. Additionally, the National Organ Transplant Act has not stated that plasma is illegal to sell, however, there is a risk of plasma being sold outside of regulated channels. Blood plasma is legally distributed by organizations like Red Cross. If someone is desperate enough for blood plasma, he or she will try to find alternative means of receiving it.

            Through future parabiosis experiments and fractioning of blood proteins, a cure for a number of degenerative diseases may be determined. Companies, like Alkahest, have attracted the attention of many. The body can regenerate plasma in about a week’s time, making this human plasma treatment attractive as an anti-aging treatment.


References

1.     Katsimpardi L, Litterman N, Schein P et al. Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors. Science. 2014;344(6184):630-634. doi:10.1126/science.1251141.

2.     Villeda S, Luo J, Mosher K et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011;477(7362):90-94. doi:10.1038/nature10357.

3.     Conboy I, Conboy M, Wagers A, Girma E, Weissman I, Rando T. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433(7027):760-764. doi:10.1038/nature03260.

4.     Baht G, Silkstone D, Vi L et al. Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin. Nature Communications. 2015;6:7131. doi:10.1038/ncomms8131.

5.     Loffredo F, Steinhauser M, Jay S et al. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell. 2013;153(4):828-839. doi:10.1016/j.cell.2013.04.015.

6.     Salpeter S, Khalaileh A, Weinberg-Corem N, Ziv O, Glaser B, Dor Y. Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication. Diabetes. 2013;62(8):2843-2848. doi:10.2337/db13-0160.

7.     Hamzelou J. Blood from human teens rejuvenates body and brains of old mice. New Scientist. 2016.

8.     Dockrill P. Scientists Have Rejuvenated Old Mice With the Blood of Human Teenagers. ScienceAlert. 2016.

9.     Blood Facts and Statistics | American Red Cross. American Red Cross. 2016. Available at: http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics. Accessed December 16, 2016.